Thermal gelation or gel melting: (ethylene glycol)₁₁₃‐(l‐alanine)₁₂ and (ethylene glycol)₁₁₃‐(l‐lactic acid)₁₂

Abstract

When PEG (M.W.5000 Daltons) is conjugated to poly(L-alanine), the polymer aqueous solutions (<10.0 wt.%) undergo sol-to-gel (thermal gelation), whereas it is conjugated to poly(L-lactic acid), the polymer aqueous solutions (>30.0 wt.%) undergo gel-to-sol (gel melting) as the temperature increases. In the search for molecular origins of such a quite different phase behavior, poly(ethylene glycol)-poly(L-alanine) (PEG-PA; EG 113 -A 12 ) and poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLA; EG 113 -LA 12 ) are synthesized and their aqueous solution behavior is investigated. PEG-PAs with an a-helical core assemble into micelles with a broad size distribution, and the dehydration of PEG drives the aggregation of the micelles, leading to thermal gelation, whereas increased molecular motion of the PLA core overwhelms the partial dehydration of PEG, thus gel melting of the PEG-PLA aqueous solutions occurs. The core-rigidity of micelles must be one of the key factors in determining whether a polymer aqueous solution undergoes sol-to-gel or gel-to-sol transition, as the temperature increases. V C 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2434-2441 KEYWORDS: sol-gel transition; block copolymers; stimuli-sensitive polymers; self-assembly; micelles INTRODUCTION Polymer aqueous solutions that undergo temperature-sensitive sol-gel transition have been extensively investigated during the last decade, not only for their biomedical applications, but also for their unique transition mechanism.1-10 Basically, the sol-gel transition is observed for aqueous solutions of polymers with a delicate balance of hydrophilicity and hydrophobicity. The sol-gel transition behavior is affected by the architecture and chemical structure of a polymer. AB-type diblock copolymers and ABA-type triblock copolymers, where A is hydrophilic and B is hydrophobic, tend to form spherical micelles, whereas BAB-type triblock copolymers tend to form flower-like micelles or intermicellar bridges.11 In addition, the molecular architecture of the block copolymer affects the secondary structure of polypeptide.12-14 Therefore, the sol-gel transition behavior can be different for the polymers with different architectures even though total molecular weight is similar. In this article, we designed AB-type diblock copolymers with the same number of repeating units to focus on the effect of ester versus amide bonds on the sol-gel transition behavior. Even though, there have been extensive reports on the poly(ethylene glycol)/poly(L-lactic acid-co-glycolic acid) (PEG/PLGA) and poly(ethylene glycol)/poly(L-lactic acid) (PEG/PLA) block